New surprise! Nature reveals: succinic acid promotes fat burning in mice

[Alliance Raws-Zoe]

Succinate, a metabolic product that promotes heat production. Scientists have recently discovered that by feeding water containing succinic acid, mice on high-fat diets can be prevented from gaining weight! They confirmed that this originally "inconspicuous" molecule promoted the burning of brown fat.
Usually, there are two ways to lose weight: eat less (reducing calorie absorption), exercise (consuming more calories). On July 18th, a new article in the journal Nature revealed a simpler way to provide an indication of the problem of obesity in humans.
Scientists at Harvard Medical School and the Dana–Farber Cancer Institute have found a “mysterious molecule”, succinate, which has been shown to activate brown fat in mice and promote fat burning.
As we all know, our body contains two kinds of fat cells with different colors: white fat and brown fat. Among them, white fat accumulates under the skin, responsible for storing excess calories and causing obesity; while brown fat burns fat to turn it into heat, which is the key to mammals' body temperature.Compared to white fat, brown fat cells contain smaller lipid droplets and more mitochondria. Mitochondria are very familiar to everyone, the main place of energy metabolism. Lipid droplets are organelles that regulate the energy balance of cells.
How to activate brown fat burning? The key issue is finding the "switch" that brown fat consumes calories. At a macro level, the answer to this question is exposure to the cold, as the cold promotes the burning of brown fat. Molecularly, scientists speculate that the brain feels cold and transmits this signal to brown fat through a process mediated by beta-adrenergic receptors.
But drugs that target this receptor have not succeeded in preventing obesity. So scientists have to find other pathways. Edward T. Chouchani of the Dana–Farber Cancer Institute and the team began by looking for metabolites specific to brown fat, which increased in cold environments. In the end, they discovered succinic acid, a metabolic intermediate in the TCA cycle.
The TCA cycle is generally considered to be a process that occurs within a cell. Therefore, most succinic acid is consumed by the same cell. However, some succinic acid will enter the bloodstream. The research team confirmed that succinic acid in the blood releases a key mechanism that promotes muscle activity, so the mice will tremble in cold conditions.
To track circulating succinic acid in the blood, the Edward T. Chouchani team injected mice with succinic acid with a heavy carbon isotope label. It was found that these succinic acids preferentially accumulate in brown fat. This means that succinic acid is associated with adipose tissue.
What's really interesting is that even drinking high-fat foods can prevent mice from gaining weight after drinking water containing succinic acid for 4 weeks. Moreover, these metabolites are dependent on UCP1 - the most beneficial metabolism of succinic acid is absent in mutant mice lacking the UCP1 protein.
Therefore, succinic acid is responsible for activating heat production and calorie consumption in brown fat.
Of course, humans are different from mice, and the most obvious difference is that humans are larger. Therefore, we are better at keeping warm than mice, but the heat is poor. Perhaps for these reasons, brown fat accounts for a much lower proportion in our bodies.In addition, as you age, brown fat will decrease. These properties may limit the metabolic activity of brown fat.
However, this research still gives us new surprises. Previously, we never thought that the intermediates of the TCA cycle were a key factor in metabolism. If succinic acid is proven to promote fat burning in the body, it will provide new ideas for solving obesity.

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